Antibodies prevented infection of the fetus with the Zika virus
Oleg Lischuk, N+1
American scientists have isolated a neutralizing human antibody against the Zika virus and with its help effectively prevented intrauterine infection in mice. Unlike experimental preventive vaccines, it proved effective even after infection of pregnant females. They report this on the pages of the journal Nature (Sapparapu et al., Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice).
To date, the epidemic of Zika fever has penetrated from South America to North America, as well as to Southeast Asia. The disease, which is quite mild in itself, causes great concern, since it can lead to dangerous complications: microcephaly (underdevelopment of the brain and skull) in children and various neurological disorders in adults. At the same time, effective antiviral therapy has not yet been developed.
In search of treatment, the staff of Vanderbilt University in Nashville and Washington University in St. Louis, as well as the biotech company Integral Molecular, isolated a set of monoclonal antibodies to the Zika virus envelope protein in people who had been infected in various regions of the world. The antibodies obtained were tested for the ability to inactivate the virus.
It turned out that the strongest neutralizing effect is the antibody ZIKV-117, which binds to the contact point of two dimers of the shell protein. In experiments, it inactivated various strains of viruses belonging to the American, African and Asian lines, and the effectiveness was maintained with six cell culture replantings (that is, the pathogen could not mutate so as to become insensitive to ZIKV-117). At the same time, the antibody did not bind to different types of dengue virus (previous studies have shown that antibodies effective against both viruses can worsen the course of dengue fever).
In experiments on mice, a single administration of ZIKV-117 on the first or fifth day after infection with a lethal dose of a highly pathogenic strain of the pathogen more than halved the mortality of animals. Administration of the antibody to pregnant mice the day before contact with the virus prevented infection of the placenta and fetal death in more than 90 percent of cases (in the control group, less than 10 percent of the offspring survived).
The administration of ZIKV-117 to pregnant females a day after infection significantly reduced the number of viruses in their brain, as well as in the placenta and fetus. This effectively prevented placental insufficiency and fetal weight deficiency.
"This is the first antiviral agent that prevented the developing fetus from the Zika virus, which serves as a fundamental confirmation of the possibility of treating infection during pregnancy," said Michael Diamond, one of the authors of the work.
As the scientists write, the results obtained allow us to proceed to testing ZIKV-117 on monkeys whose placenta device is closer to a human one. If successful, it will be possible to start clinical trials of a therapeutic antibody. In addition, the detected binding site on the envelope protein of the virus may help in the development of a preventive vaccine against Zika fever.
Zika fever was first detected in 1947 in Uganda. In May 2015, the spread of the virus began in the northeast of Brazil. To date, the epidemic of the disease has been recorded in dozens of countries in South and North America and Southeast Asia.
In February 2016, WHO recognized the Zika virus as a global threat to public health due to the sharply increased risk of microcephaly after infection during pregnancy. Studies have shown that this effect of the virus is associated with its ability to infect the progenitor cells of neurons. The mechanism of its penetration through the blood-brain barrier was also described and two viral proteins (NS4A and NS4B) responsible for brain damage were identified.
According to the latest forecasts, by the end of the first wave of the epidemic, more than 93 million people will be infected with Zika fever, including about 1.65 million pregnant women.
In June 2016, the US Food and Drug Administration (FDA) approved clinical trials of the first experimental vaccine against the Zika virus, called GLS-5700, which was developed by the American company Inovio Pharmaceuticals and the Korean GeneOne Life Science. On November 7, the first trials of a preventive vaccine containing an inactivated virus began in the United States.
Recently, an international research team named the existing antiviral drug sofosbuvir as a possible means of preventing microcephaly in Zika fever, but its tests for this indication have not yet been conducted.
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10.11.2016